Primary hyperparathyroidism is a different disease today than it was severa decades ago. It is now a relatively common endocrine disorder with few of the obvious features by which it used to be known. Previously held concept about primary hyperparathyroidism need careful reevaluation in light of its current profile, using newer techniques to monitor the skeleton, a major target organ for parathyroid hormone. The overall objective of this research project is to characterize modern primary hyperparathyroidism with respect to extent, course and reversibility of its manifestations. The prospective, long-term study is in the midst of obtaining information pertinent to five specific aims: 1. to provide a complete description of th current clinical presentation of primary hyperparathyroidism through clinical, biochemical, densitometric and histomorphometric analyses; 2. to determine the natural history and reversibility of primary hyperparathyroidism with long-term evaluation of clinical, biochemical, densitometric and histomorphometric indices; 3. to establish by histomorphometric analysis of bone, the mechanisms of cancellous bone preservation and cortical bone loss in primary hyperparathyroidism; 4. to determine the utility of non-invasive markers of bone turnover as indicator of processes in hyperparathyroid bone; 5. to establish the course and reversibility of primary hyperparathyroidism in the skeleton of postmenopausal women. Patients are evaluated as an entire study cohort and also from the viewpoint of different clinical subgroups. The project utilizes state-of-the art techniques for evaluation of the effect of parathyroid hormone on the skeleton. These techniques, including bone densitometry, histomorphometric analysis of bone, and highly promising circulating and urinary markers of bone metabolism, are combined with more conventional clinical assessments of patients. A substantial number of patients already have been enrolled, and many have been followed since 1985 With its prospective design, the research project is uniquely positioned to make systematic observations on primary hyperparathyroidism over a thirteen year period. In the renewal period, this investigation will continue to contribute insights into primary hyperparathyroidism, helping to establish guidelines so that the modern approach to patients with this disorder can b more rational and more secure.